Lesson 11 Neurodermatoses. Atopic dermatitis. Prurigo. Urticaria. Etiology, pathogenesis. Classification. Clinical features. Diagnostics. Treatment. Prevention.

1. Theme urgency

The group of neurodermatoses comprises diseases which begin with very severe itching and often with neurotic disorders continuing throughout the disease. They include prurigo, skin pruritus, urticaria, angioneurotic oedema, atopic dermatitis and various forms of neurodermitis.

Atopy is a state in which an exuberant production of IgE occurs as a response to common environmental allergens. Atopic subjects may, or may not, develop one or more of the atopic diseases such as asthma, hay fever, eczema and food allergies, and the prevalence of atopy is steadily rising.

In Scotland, as many as 8% of children under 2 years have visible atopic dermatitis. At least 1 schoolchild in 10 in Europe now suffers from atopic dermatitis and this figure is still rising. The reasons for this are not yet clear, but are unlikely to be a change in the genetic pool in the population. However, several environmental factors have been shown to reduce the risk of developing atopic disease.

Urticaria is a disease of allergic and toxic genesis characterized by urticarial eruptions on the skin and less frequently on the mucous membranes. Quincke's disease – acute circumscribed oedema. In oedema of the larynx, stenosis and asphyxia may occur. In localization of oedema in the region of the orbits, the eyeballs may be displaced medially and acuity of vision is reduced.

2. Concrete Objectives:

Students must know:

1. Etiology and pathogenesis of atopic dermatitis (neurodermatoses, prurigo, skin pruritus, urticaria).

2. Classification of atopic dermatitis (neurodermatoses, prurigo, skin pruritus, urticaria).

3. Clinical features of atopic dermatitis (neurodermatoses, prurigo, skin pruritus, urticaria).

4. Morphology of atopic dermatitis (neurodermatoses, prurigo, skin pruritus, urticaria).

5. Investigations of atopic dermatitis (neurodermatoses, prurigo, skin pruritus, urticaria).

6. Diagnosis of atopic dermatitis (neurodermatoses, prurigo, skin pruritus, urticaria).

7. Treatment of atopic dermatitis (neurodermatoses, prurigo, skin pruritus, urticaria).

Students should be able to:

1. To collect the medical history of patient with atopic dermatitis (neurodermatoses, prurigo, skin pruritus, urticaria).

2. To diagnostic atopic dermatitis (neurodermatoses, prurigo, skin pruritus, urticaria) in patient in typical case.

3. To prescribe the treatment for patient with atopic dermatitis (neurodermatoses, prurigo, skin pruritus, urticaria) in typical case.

4. To recommend preventive measures for patient with atopic dermatitis (neurodermatoses, prurigo, skin pruritus, urticaria).

3. Tasks for self-study during preparation for lesson.

3.1. Theoretical questions for the lesson:

1. Etiology and pathogenesis, clinical picture, diagnosis, of atopic dermatitis.

2. Treatment (general measures, external treatment, physiotherapy) and prevention of atopic dermatitis.

3. Classification of neurodermatoses.

4. Skin pruritus.

5. Etiology, pathogenesis, clinical picture, diagnosis, differential diagnosis, treatment and prevention of neurodermitis (circumscribed and diffuse).

6. Treatment (general measures, external treatment, physiotherapy) and prevention of neurodermitis (circumscribed and diffuse).

7. Etiology, pathogenesis, clinical picture, diagnosis, treatment of prurigo.

8. Etiology and pathogenesis, clinical picture, diagnosis, treatment and prevention of urticaria.

The subject-matter:

NEURODERMATOSES

The term 'neurodermitis' was introduced in 1891 by Brocq and Jacquet who regarded these diseases as skin neuroses with characteristic intense itching and subsequent development of lichenification of the skin.

In the literature, diffuse neurodermitis is usually designated 'atopic dermatitis' emphasizing the congenital nature of the disease. Coca coined word “atopy” in 1923 to mean “out-of-place-ness” or “different”. Atopy refers to predisposition to develop asthma, allergic rhinitis, and an associated skin disease appropriately called “atopic dermatitis” and referred to by many lay people simply as “eczema”. Atopic patients typically have blood and tissue eosinophilia, increased IgE responses, increased transepidermal water loss, exquisite sensitivity to pruritic stimuli (e.g., wool sweaters) and immune system dysfunction.

The subsequent understimulation of gut-associated lymphoid tissue may predispose to atopic sensitization to environmental allergens. The circulating T lymphocytes of children destined to develop allergies shift to a type II response and are poor at producing -interferon (IFN-); this persists into late childhood. Early infections may lower the risk of allergy by boosting the production of INF-.

70% of patients with atopic dermatitis have a family history of at least one of the three atopic disorders. The incidence of atopic dermatitis has risen from 2% in those born after 1970; the reason is unknown. Patients have inherently irritable (sensitive) skin in which scratching is responsible for many objective changes. Psychological, climactic, and immunologic factors may modify these changes.

A strong genetic component is obvious, although affected children can be born to clinically normal parents. The concordance rates for atopic eczema in monozygotic and dizygotic twins are 86% and 21%, respectively; and atopic diseases tend to run true to type within each family. In some, most of the affected members will have eczema; in others respiratory allergy will predominate. There is also a tendency for atopic diseases to be inherited more often from the mother than the father. Probably the inheritance of atopic eczema requires genes that predispose to the state of atopy itself, and others that determine whether it is asthma, eczema or hay fever that occurs. One plausible gene for the inheritance of atopy itself lies on chromosome 11q13. It encodes for the E subunit of the high affinity IgE receptor, which is found both on mast cells and on antigen-presenting cells in the skin. However, it has to be pointed out that several groups have failed to confirm this linkage either in the families of those with atopic eczema or respiratory allergy. Most recently, another gene strongly linked to atopic eczema has been found on chromosome 3q21. It encodes for cluster of differentiation (CD) antigens 80 and 86. Other candidates lie on chromosomes 14q, 16p and 17p.

Three of four clinical features must be present to make the diagnosis:

• Pruritus – the primary symptom and even referred to as the “primary lesion” by some;

• Typical morphology and distribution of lesions for age;

• Chronic or chronically relapsing course;

• Personal or family history of asthma, allergic rhinitis, or atopic dermatitis.

Atopic dermatitis may present at any age, but 60% of patients experience their first outbreak by their first birthday, and 90% by their fifth. Four clinical phases are recognized:

Infantile phase (2 mon. – 2 yrs): Characterized by intense itching, erythema, papules, vesicles, oozing, and crusting. Patients typically develop eruptions on the cheeks, forehead, and scalp, with less involvement of the trunk or extremities. The diaper area is usually spared. Dermatitis clears in half of the patients by 3 years of age.

Childhood phase (3 – 11 yrs): More chronic, lichenified scaly patches and plaques that may have crusting and oozing. Classic areas include the wrists, ankles, backs of the thighs, buttocks, and antecubital and popliteal fossae, although other areas, including extensors, may be involved in early childhood. Two-thirds of patients clear by age 6.

Adolescent/young adult phase (12-20 yrs): Thick, dry, lichenified plaques without weeping, crusting, or oozing that involve the face, neck, upper arms, back, and flexures.

Adult phase (>20 yrs): Most commonly involves the hands, sometimes the face and neck, and rarely diffuse areas. Only 10% of infantile or childhood cases of atopic dermatitis persist into adulthood.

With atopic dermatitis may be associated such physical findings:

• Dry skin – due to decreased ability to bind and retain water in the skin.

• Vascular abnormalities – skin pallor, low finger and toe temperatures, pronounced vasoconstriction on exposure to cold.

Excessive washing without appropriate skin lubrication is the most common irritant, as repeated water exposure degrades the skin’s barrier to external irritants and internal water loss. Important topical irritants include wool, synthetic fabrics, poorly fitting clothes, mineral oils, solvents, sand, and excessive perspiration. Airborne particles, such as tobacco smoke, animal dander, molds, and house dust mites exacerbate disease in some patients, especially infants with severe dermatitis. Secondary infections due to Staphylococcus aureus or Pityrosporum orbiculare may also aggravate the disease. Allergies to milk, eggs, nuts, soybean products, wheat, and seafood have been implicated by some researchers, but their true role in atopic dermatitis remains controversial. Food elimination diets have no proven benefit. Some studies suggest that breastfeeding reduces the incidence of atopic dermatitis in the first year of life, while others have not demonstrated a difference.

A variety of measures can control atopic dermatitis:

• Avoid provoking factors (scrubbing, too frequent bathing, scented soaps, etc.).

• Reduce dryness and pruritus by applying emollients to moist skin, add moisture, and lubricate. Use mild, unscented soaps only on hairy or oily areas, and water only to bathe other areas. Avoid overbathing and apply moisturizer within 3 minutes of exiting the bath or shower to retain moisture added from bathing.

• Wear cotton clothing as much as possible, and if the arms and forearms are affected, wear long-sleeved shirts to reduce evaporation from the skin.

• For subacute or chronic lesions, topical corticosteroids are the mainstay of therapy. Typically, younger patients require less potent steroids and vice versa.

• Oral or topical antipruritic agents may be helpful. Oral antihistamines may help because of their sedating effects.

• If lesions are secondarily infected, antibiotic therapy for at least 2 weeks should be prescribed. There is some evidence that toxins and/or superantigens produced by S. aureus induce dermatitis in some patients and that antibiotics may have a role in atopic patients not responding to standard therapy.

• Tacrolimus (effective topically) used to treat atopic dermatitis and UVB, and PUVA are also effective for more severe cases of atopic dermatitis.

• Topical steroids should be used on lesions. Lesions get infected because the skin defense barrier is broken. The topical steroids allow it to heal and thus the bacteria have greater difficulty infecting the skin. Such bacteria have receptors for fibrin or fibronectin that can be exposed in dermatitic, but not normal, skin.

The following classification of neurodermatoses is accepted in Russian and Ukraine literature:

1. Skin pruritus (localized, generalized);

2. Neurodermitis (localized, diffuse);

3. Prurigo (infantile, adult, nodular);

4. Urticaria (chronic).